The references discussed herein are provided solely for the purpose of describing the field relating to the invention. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate a disclosure by virtue of prior invention.
Zein is a plant protein isolated from corn or maize and belongs to a family of prolamines which are composed of high amounts of hydrophobic amino acids, such as proline, glutamine and asparagine. Zein is clear, odorless, non-toxic, biodegradable and water-insoluble. Zein has been investigated and used as a polymer in the pharmaceutical, medical, food, cosmetic, adhesive and packaging industries.
In the food and pharmaceutical industries, zein has been used, for example, to film-coat materials and to form particulate systems such as microparticles or nanoparticles [1-5]. Various methods of forming zein particles have been proposed. For example, U.S. Pat. No. 5,330,778, the contents of which are incorporated herein, discusses a method for preparing microparticles using zein, and uses pH alteration to form the zein microparticles [6]. However, the method described in U.S. Pat. No. 5,330,778 produces zein particles with larger micron sizes and with a wide particle size distribution, which has significant drawbacks, for example, for in vivo use.
It is important to ensure that a biomaterial used for human or animal applications is safe and non-immunogenic. In general, upon in vivo administration (e.g., introduction into the body) of particles, phagocytic cells in the blood and tissues, which are responsible for immunological recognition and removal of foreign particles, can initiate an immune response depending on the physicochemical characteristics of the particles. The uptake by phagocytic cells is dependent on both particle size and surface hydrophobicity of the foreign particle. In general, particles in a diameter size range greater than approximately 500 nm are prone to phagocytosis. Particles with a hydrophobic surface are easily recognized by the phagocytic cells [7]. For example, Lopez and Murdan [8] have recently reported that zein microspheres of a diameter of 1.36±0.036 are immunogenic and, consequently, are not suitable as a drug, vaccine or other therapeutic carrier.